The aim of this project is to improve the identification and classification of depressed patients by incorporating biologic variables into the clinical diagnostic procedure. We have developed a neuroendocrine research strategy, focused on the limbic system regulation of hypothalamus-pituitary-adrenal cortical (HPA) function. Pilot studies have shown that severe HPA disturbances are found in "endogenomorphic" depressives (bipolar, unipolar) but not in neurotic depressives or other psychiatric patients. By testing HPA regulation with a dexamethasone suppression procedure, we have identified a large subgroup of depressives at confidence levels approaching 100%. The test may be especially useful with patients who have unclear clinical presentations. Preliminary multivariate analyses suggest that addition of detailed clinical features will result in improved classification of subjects. The proposed work will extent and improve upon the pilot studies. We shall use the dexamethasone test in both inpatients and outpatients, and collect detailed clinical data. By measuring plasma and urinary cortisol, after various doses of dexamethasone, we aim to confirm the specificity of our pilot study findings and to provide a simple laboratory procedure which can be used in the clinical evaluation of depressives.